CN113645915A

CN113645915A - Method and system for monitoring tissue ablation by constrained impedance measurements

Info

Publication number: CN113645915A
Application number: CN202080027495.0A
Authority: CN
Inventors: P·钱; M·A·巴尔里; A·麦克伊文; D·M·阮
Original assignee: University of Sydney; Western Sydney Local Health District
Current assignee: University of Sydney; Western Sydney Local Health District
Priority date: 2019-04-02
Filing date: 2020-04-02
Publication date: 2021-11-12
Also published as: EP3946114A1; EP3946114A4; CA3134712A1; WO2020198796A1; AU2020254707A1; JP2022526075A; US20210401495A1

Abstract

A system for monitoring tissue lesion development during a medical ablation procedure, comprising: a catheter ablation device having at least one catheter electrode, the catheter ablation device configured to apply ablation energy to ablated tissue in a target region; a plurality of external electrodes for application to a patient's body; and a measurement circuit for determining an electrical characteristic of a current path between the at least one catheter electrode and the outer electrode without application of the ablation energy. The use of the method may comprise: alternating between an ablation phase involving delivery of ablation energy and a measurement phase involving measuring electrical characteristics of a current path through a lesion region formed by ablation, wherein the two phases are sequentially repeated until analysis of the measurements indicates that a desired lesion size is obtained.

Description

Method and system for monitoring tissue ablation by constrained impedance measurements

Technical Field

The present invention relates to methods and systems for monitoring tissue ablation by constrained impedance measurements. It finds particular application in the real-time continuous assessment of intravascular cardiac catheter ablation therapy, but may equally find application in a variety of other medical treatment techniques.

Background

Cardiac catheter ablation, such as Radio Frequency (RF) ablation, is capable of treating a wide range of arrhythmias in a minimally invasive manner and constitutes a rapidly growing field in interventional cardiology. The cardiac regions involved in these arrhythmias may be reached via access from a peripheral vein or artery with a catheter equipped with a suitable ablation device, such as an RF radiation electrode or other suitable instrument, and may be ablated by applying ablation energy to heat the tissue.

RF catheter ablation involves the delivery of high frequency alternating current (in the range of 350kHz to 1 MHz) through one or more electrode catheters to the myocardial tissue to create thermal damage. The mechanism of current heating of tissue is resistive (ohmic) heating of the narrow edges (<1mm) of the tissue in direct contact with the electrodes, with deeper tissue regions heated by conduction. Heat is dissipated from this area by further heat conduction into the normothermic tissue and by thermal convection through the circulating blood pool.

Too small an injury may be ineffective in treating arrhythmia, while too large an injury may be associated with undesirable complications. Overheating in this area is a major problem with potential risks including puncture and tamponade. Thus, successful catheter ablation requires not only precise positioning of the arrhythmogenic substrate, but also complete and permanent elimination of the substrate without collateral damage.

Although there is a need to monitor lesion development during ablation procedures, there is currently no reliable means to achieve this clinically. Alternative measurements (such as catheter tip temperature and impedance changes, ablation power, duration, catheter tip pressure, and reduction of intracardiac electrocardiogram recorded on the ablation catheter) may provide an indication that the catheter tip is properly positioned relative to the heart wall and ablation is occurring, but generally cannot provide any direct measurement of lesion formation or development. MRI can provide high resolution images of lesions with relatively little error, but the image reconstruction times are long (up to 30 minutes), so this technique is not feasible for standard clinical procedures.

Previous systems for determining lesion size include the use of Electrical Impedance Tomography (EIT). EIT is affected in its traditional implementation because it is an ill-defined method that produces low spatial resolution results. Thus, the system of EIT delivery relies heavily on CT imaging or location information throughout the treatment, which is utilized in addition to real-time catheter location knowledge.

There is a need for a more reliable system and method for monitoring lesion development during catheter ablation without numerical solutions for EIT or without having to resort to CT information.

The reference to any prior art in this specification is not an acknowledgement or suggestion that prior art forms part of the common general knowledge in any jurisdiction or that prior art could reasonably be expected to be combined with any other prior art by the skilled reader.

Disclosure of Invention

During the delivery of electromagnetic radiation in a catheter ablation procedure, temperature changes in the heart tissue due to resistive and conductive heating are accompanied by changes in the organized electrical impedance. Theoretically, as the temperature increases, the impedance decreases. This allows real-time measurement of heating in the tissue volume by measuring the changing impedance of the tissue volume.

According to the present invention, in a first aspect, there is provided a system for monitoring the development of a tissue lesion during a medical ablation procedure applied to a patient, the system comprising:

a catheter ablation device having at least one catheter electrode;

the device is connectable to a source of electrical energy via an electrical feed line and is configured to apply ablation energy to ablate tissue in a target region;

a plurality of external electrodes for application to a patient's body;

a measurement circuit for determining an electrical characteristic of a current path between at least one catheter electrode and an external electrode without application of the ablation energy; and

an electrical controller.

Preferably, the electrical characteristic is the impedance of the current path.

In a preferred form, the electrical controller is arranged to control application of the AC current source between different combinations of the at least one catheter electrode and the plurality of external electrodes such that the resulting measurements of voltage can provide measurements of the impedance of different electrical paths through the patient's body between the respective electrodes, and the electrical controller is further configured to disconnect or otherwise halt said application of ablation energy from the source of electrical energy during application of said AC current source.

The system may include a virtual resistive load for selectively connecting to a source of electrical energy during an operational period of the measurement circuit. In this case, an ablation shunt (shunt) may be included that is configured to decouple the energy source from the catheter ablation device and couple it to the virtual load.

Alternatively, an intermittent source of electrical energy may be used, which may be quickly shut down during the period when the measurement is being made.

In a preferred form, the measurement circuit comprises a switch matrix arranged for switching between different electrode combinations under the control of the electrical controller.

Preferably, the measurement circuit is configured to perform four-terminal sensing to measure the electrical characteristic (e.g., impedance).

The electrical controller may comprise a PC. In a preferred form, the measurement circuit includes one or more analog-to-digital converters (ADCs) to provide a digital representation of the measured voltage. In one embodiment, a plurality of ADCs is included for measuring different current paths simultaneously, each ADC being arranged to switch between different selected external electrodes under the control of the electrical controller.

In one form, the source of electrical energy is an RF generator. The present invention may also be applied to other types of ablation procedures, including microwave ablation and electroporation.

The plurality of external electrodes may be configured as a dot harness for application across an external region of a patient's body.

According to the present invention in a second aspect there is provided a method of operating a system for monitoring the size of a lesion during a catheter ablation procedure applied to tissue of a subject, the method comprising:

(a) performing an ablation stage involving delivery of ablation energy to the catheter-electrode;

(b) performing a measurement phase involving measuring an electrical characteristic of a current path through a lesion region formed by ablation;

wherein steps (a) and (b) are repeated sequentially.

In a preferred form, steps (a) and (b) are repeated sequentially until the measurement performed in step (b) indicates a specified lesion size.

In step (b), ablation energy may be transferred from the catheter-electrode to the dummy load.

The method of the second aspect of the invention may comprise using the system of the first aspect of the invention, wherein step (a) is performed using the catheter ablation device, and step (b) is performed using the plurality of external electrodes and the measurement circuitry, the switching between steps (a) and (b) being performed under control of the electrical controller.

Thus, according to the method, the measurement phase involves sequentially passing a current between one or more catheter electrodes and a plurality of electrodes applied outside the patient's body and measuring the electrical response. Analysis of the results provides an assessment of the effect of the most recent ablation stage, and analysis of the results of successive measurement stages allows prediction as to the desired lesion size obtained.

The method may include an initial determination phase in which one or more current paths are selected from a plurality of current paths by sequentially applying current between one or more catheter electrodes and a plurality of external electrodes applied to the patient's body and measuring the electrical response, and the electrode for step (b) is selected in dependence on the result.

Preferably, a prescribed number of current paths are selected in the determination phase, wherein the associated electrodes are used for subsequent iterations of step (b).

In one embodiment, the electrodes are selected as those associated with the lowest impedance of the current path being measured. Alternatively, the electrodes may be selected to be those associated with current paths that are most sensitive to local state changes of the patient's body, such as injecting a conductive solution into the area adjacent to the lesion.

The change in impedance may be compared to previously determined data (e.g., in a look-up table) to provide a measure of lesion size to the medical practitioner. Tests have shown that the method of the invention can be used to track lesion size within an error of only about 1mm deep and 3mm long, which is considered clinically acceptable in most applications.

In a preferred form, the method includes using the measurements made in step (b) in an algorithm to estimate the size of the lesion formed in step (a).

In one embodiment, for each measurement phase, the measurement results are analyzed and a selection is made of which measurements to use in the algorithm.

The selection may be made based at least in part on a change in an electrical characteristic of the associated current path since a previous measurement phase. For example, the selection may be based on the maximum impedance drop caused by the ablation phase of the intervention.

In a preferred form, step (a) and/or step (b) may be gated by the subject's respiratory cycle and/or heartbeat, so that the measurement phase is performed at a relatively stable point.

The algorithm used in the analysis of the measurements may comprise a regression analysis algorithm. Alternatively or additionally, machine learning may be used to interpret the results. As will be appreciated, analysis of the results (particularly based on the position of the external electrode for each measurement) may be used in the determination of lesion size, lesion shape and/or lesion orientation.

Accordingly, the present invention relates to impedance measurement between an ablation catheter electrode and a plurality of external electrodes. In the present description and claims, the term "outer electrode" is used to refer to the set of secondary electrodes that are remote from the catheter. In a common application, the external electrode is placed outside and in contact with the patient's body. However, it will be appreciated that they may be placed within internal structures of the body, such as the esophagus, coronary sinus, or other suitable site. The catheter electrode and the external electrode are used to quickly and reliably find the clinically most important current path and to obtain a measurement of the impedance change as ablation proceeds, which can provide a clinically useful indication of lesion growth.

The use of multiple impedance measurements between multiple electrodes in different locations on a patient's body is of course known in the general field of EIT. However, EIT is used for medical imaging, particularly in areas such as monitoring lung function, localization of cancerous regions, brain activity and localization of gastric activity. Rather, the present invention does not rely on image reconstruction software, but instead uses a combination of electrode(s) included in the ablation catheter with a plurality of external electrodes and specially configured switching devices to determine which set of electrodes (corresponding to a particular conductive path) to use in continuously monitoring the effectiveness of the ablation catheter's use, the response in the measured electrical characteristics of these current paths providing a relatively direct, real-time indication of lesion formation progress. As with EIT, the current applied in the method of the invention is typically relatively small and at a suitably high frequency to avoid significant nerve stimulation or ohmic heating within the body. Unlike using EIT to monitor lesion formation, the present invention does not require complex computational solutions and does not require recourse to CT imaging or location information.

The proximity of the catheter electrode(s) establishes that the heated volume is included in the resulting electrical path to the outer electrode(s), and according to the invention, the most suitable current path is found by iteratively applying currents on the plurality of electrodes and performing voltage measurements. A prescribed criterion, such as the lowest calculated impedance measurement, is considered to be an indication of the most appropriate path for monitoring lesion formation during ablation therapy.

Drawings

Other aspects of the invention and other embodiments of the aspects described in the preceding paragraphs will become apparent from the following description, given by way of example and with reference to the accompanying drawings, in which:

fig. 1 is an overview of a system for monitoring lesion development during RF catheter ablation of a patient according to one embodiment of the present invention.

Fig. 2 depicts an ablation interface of the system of fig. 1 connected to an RF generator.

Fig. 3 depicts an alternative interface to the system.

Fig. 4 is a flow chart illustrating a method for monitoring lesion development during catheter ablation according to one embodiment of the present invention.

Fig. 5 is a flow chart of a measurement phase of the method shown in fig. 4.

Fig. 6 is a flow chart illustrating a method for monitoring lesion development during catheter ablation in accordance with an alternative embodiment of the present invention.

Fig. 7 is a flow chart of a measurement phase of the method shown in fig. 6.

Fig. 8 shows an embodiment of 64 ECG electrodes ("spot electrodes") arranged in 16 four strips.

Fig. 9 is a schematic view of a catheter device and an ablation lesion.

Detailed Description

It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the present invention.

The system 10 shown in fig. 1 provides monitoring of lesion development during RF catheter ablation and comprises an RF ablation catheter 3 (comprising an RF radiator and an RF power supply line) for introduction into a heart chamber of a patient 11. The catheter 3 is provided with catheter electrodes E1, E2, E3, E4, electrode E1 comprising an RF ablation electrode (see fig. 9), while the patient return electrode 2 is attached to the patient's thigh or other suitable location. As discussed further below, the straps 4 of the outer surface electrodes 1 wrap around the chest of the patient. The outer electrode 1 may be a conventional ECG point electrode, in which case it is used to measure voltage.

The ablation catheter 3 may be, for example, a 3.5mm Fr thermoool catheter (Webster Inc.) Webster bio functional, a Therapy Cool Flex ablation catheter or any other suitable device known to those skilled in the art. The ablation generator 12 may be, for example, a Stockert 70 cardiac ablation radio frequency generator St4520 (webster biofunctional).

The electrical interface module 6 (also labeled 6A with respect to embodiment 2 of the present invention, discussed further below) includes a plurality of relays and N-way switches (e.g., switch matrix 16/16A, included in impedance measurement circuit 17/17a (see fig. 2 and 3)), the electrical interface module 6 being configured to manage an ablation phase and a measurement phase of a treatment of the patient 11.

The switch control is provided by a PC running a customized computer program (not shown). The output of the RF generator 12 is referred to as input 5 of the interface module 6/6 a. In addition, interface module 6/6a is electrically connected to patient return electrode 2 by lead 9, to each outer electrode 1 of electrode strip 4 by outer electrode lead 8, and to each inner electrode E1, E2, E3, E4 of catheter 3 by lead 7 by means of cable connector 13.

Additionally, the system may further comprise a real-time ECG/QRS (heartbeat) detector 102, the ECG/QRS (heartbeat) detector 102 having ECG electrodes 101 placed on each wrist of the patient. The ventilator 100 may be used to ventilate an anaesthetised patient 11 during an ablation procedure, in which case the ventilator 100 is configured such that the breathing cycle measurements are received by the computer program. Alternatively, if the patient 11 is only sedated, a signal indicative of respiratory function received from another source, such as fluctuations in thoracic wall impedance, may be used.

Example 1

A first embodiment of the circuitry of the electrical interface module 6 connected to the RF generator 12 is shown in figure 2. The ablation shunt 24, relay 19, and relays in the

relay banks

20, 21, 22 (collectively referred to as relay banks 23) are shown in an impedance measurement position. The N-way switches of switch matrix 16 are shown as being disposed at arbitrary positions, however during a "measurement phase" the switches will cycle through multiple positions, as described in detail below.

The switch matrix 16 is made up of four N-way steering switches 18A, 18B, 18C, 18D. In the example configuration, switches 18A and 18B are 4-way switches, with the throw of each switch providing a connection to each of the conduit electrodes E1-E4.

Switches

18C and 18D are 64-way switches, but only four terminals are shown for ease of depiction. The throw of

switches

18C and 18D provides a connection to each of the 64 outer surface electrodes 1. Together, these N-way steering switches 18A, 18B, 18C, 18D allow the AC constant current source 15 and the terminals of the high precision voltmeter 14 (with outputs via the ADC) to be selectively connected to any of the catheter electrodes E1-E4 and the external electrode 1.

The appropriate operating frequency of the AC current source 15 is used, as determined based on competing factors. The frequency must be high enough to avoid tissue stimulation and allow several measurement cycles to be acquired in a short period of time, but low enough to minimize the effects of parasitic capacitance within the catheter and to minimize any interference from the frequency of application of the ablation energy. In initial tests, the inventors found that frequencies in the range of 50kHz to 100kHz were preferred. The amplitude of the injected current is also suitably selected, as determined by competing factors. Higher currents provide better voltage resolution, especially for low impedance paths, however the current should not be so high that the electrodes themselves begin to heat up. In initial tests, the inventors found that currents in the range of 2-5mA were preferred.

Thus, the measurement circuit 17 is configured to perform sequential four-terminal impedance measurements. To perform each measurement, a current is supplied between the first catheter electrode E1/E2/E3/E4 and the first external electrode 1, and the resulting voltage is measured between the second catheter electrode and a second external electrode adjacent to the first external electrode. The resulting impedance is then passed from the USB output of the ADC voltmeter 14 to an external PC (not shown).

In the example configuration shown in fig. 8, the electrode strip 4 consists of four rows of 16 outer "dot" electrodes 1. The electrode groups immediately adjacent to electrodes "a" and "b" are indicated by dashed and dotted outlines, respectively. As will be noted, electrode "a" (e.g., all other electrodes in the upper or lower row) has five directly adjacent electrodes, while electrode "b" (e.g., all other electrodes in the center row) has eight directly adjacent electrodes. The electrode belt 4 is shown as flat in figure 8, but it will be appreciated that in use it wraps around the chest of the patient so that the leftmost and rightmost electrodes depicted become mutually adjacent electrodes.

As an example four terminal arrangement, obtaining an impedance measurement in the conductive path between the catheter 3 and the electrode "a" is achieved by connecting the positive terminal I + of the current source 15 to the catheter electrode E3, the negative terminal I-of the current source 15 to the external electrode "a", the positive terminal V + of the ADC voltmeter 14 to the catheter electrode E2, and the negative terminal V-of the ADC voltmeter 14 to any one of the five external electrodes 1 adjacent to the electrode "a". Thus, any one of the five measurements may provide a determination of the current path to the catheter associated with electrode "a", and the method of the present invention uses all five measurements to determine the most appropriate. The same applies to any electrode in the upper or lower row of electrode strips 4.

Similarly, for electrode "b" (or any other electrode in any of the middle rows of electrode strip 4), any of the eight measurements may provide a determination of the current path to the catheter associated with that electrode, and the method of the present invention uses all eight measurements to determine the most appropriate. The impedance measurement is further discussed below with reference to the calibration phase and the measurement phase of the method of the present invention.

Returning to fig. 2, the ablation shunt 24 is comprised of two SPDT (single pole double throw) relays 19 that operate simultaneously to direct electrical ablation power from the RF generator 12 to the catheter electrode E1 and the return electrode 2, or to a dummy load 25 (e.g., a 10 Ω resistor) while a measurement is being performed. The SPDT relay 19 may be, for example, a G6EK-134P-ST-US-DC5 (ohm dragon electronic assembly) relay. This arrangement provides protection for the measurement circuitry 17 and other components from high voltages and RF noise.

Further, ablation

isolation relay banks

20, 21, 22 (collectively referred to as relay banks 23) are arranged to operate in synchronization with ablation shunt relays 19. During ablation, the grounding relay 20 connects the throws of the N-way switches of the switch matrix 17 to ground. Isolation relay 21 isolates external point electrode 1 from catheter electrodes E2-E4. Relay 22 connects catheter tip electrode E1 and the return electrode to the respective throws of the ablation shunt relay.

In one state (where impedance measurements can be made), relay sets 20 and 21 together allow connection from the throw of

switches

18A, 18B to each catheter electrode E1-E4 and from the throw of

switches

18C, 18D to each external electrode 1, while return electrode 2 is disconnected from catheter tip electrode E1 (as shown).

Thus, the ablation shunt relay 19 and the ablation isolation relay of the relay bank 23 enable the system to switch between two states (i.e., an ablation state and a measurement state). The method of the present invention involves an iterative process that loops between these two states, and the present embodiment with respect thereto is discussed below with reference to fig. 4.

The process shown in fig. 4 involves a setup phase followed by a determination phase followed by repeated ablation and measurement phases that continue until the desired lesion size is achieved (as determined using voltage/impedance measurements), at which point the treatment is stopped.

Setting phase

The first step of the process is a setup phase 41 during which the AC current source 15 and ADC voltmeter 14 are used to obtain a four terminal internal to external voltage measurement using each of the two electrodes of the conduit 3 and the external electrode 1. The purpose of the setup phase is to take measurements of all possible electrical paths between the inner and outer electrodes to allow determination of the best path for the measurement being made. As will be appreciated, for injection of a known current, the measured voltage provides a determination of the impedance of the current path.

As discussed above, voltage measurements resulting from the applied current are obtained for the electrical path between the catheter and the external electrode. Ablation catheters (e.g., webster biofunctional thermoool ablation catheters) typically have four catheter electrodes, however only two internal electrodes are required for four terminal voltage measurement. In the described example, E2 and E3 were used to perform measurements, where E1 was used only for ablation and E4 was not used. The inventors believe that E4 is too far from the catheter tip, and tests have shown that in practice impedance measurements using E1 tend to be undesirable noise, possibly due to limitations in the isolation provided by the ablation shunt 24 from the RF signal to E1.

Returning again to FIG. 2, to obtain a four terminal impedance measurement, I + is connected to catheter electrode E3, V + is connected to catheter electrode E2, I-is connected to the first external electrode 1, and V-is connected sequentially to each electrode adjacent to the first external electrode. The resulting voltage measurements for each were recorded. I-is then switched to connect to the second external electrode 1, wherein V-is sequentially switched to the electrodes adjacent to this second external electrode. This continues until a current has been applied and the resulting voltage of all external electrodes is measured and recorded.

As described above, a plurality of four-terminal voltage measurements are made for each external electrode 1, which involves electrodes adjacent to each external electrode. In the configuration shown in fig. 8 (band 4 consists of 64 electrodes arranged in four rows of 16 electrodes each), a total of 416 impedance measurements and paths are recorded (five for each electrode in the top and bottom bands and eight for each electrode in the middle band).

Determining ablation measurement paths

Returning to fig. 4, the process then proceeds to a determination step 42, where the results from the setup phase are analyzed to make decisions regarding the 10 most appropriate catheter-to-external electrode paths.

The "best" path is considered to be the path of lowest impedance, since lower impedance generally indicates a more direct path and associated lower noise risk. However, it will be appreciated that in alternative approaches, other criteria may be used.

For example, the path may be selected to exhibit the highest sensitivity to the introduction of a suitable saline solution to the catheter site.

As discussed further below, rather than selecting a single inner-to-outer electrode path, step 42 involves determining 10 paths such that if a path is found to be unreliable (e.g., due to the presence of lung fields), other measurement paths are available. As the skilled reader will appreciate, any number of internal to external electrode paths may be selected, and the inventors have determined that ten paths provide a suitable and viable number of alternatives for the method of the present invention. As will be appreciated, selecting more paths will involve longer monitoring times, while selecting fewer paths may introduce random errors.

In an alternative approach discussed below with respect to embodiment 2 of the present invention, rather than determining a limited number of paths for impedance measurement during the ablation process, all path impedances may be measured at each measurement stage, with the determination of which paths to use in the analysis being made according to a specified criterion.

Ablation stage

Once the determination step 42 is completed, the RF ablation treatment is started (ablation stage 43). As discussed above, during this phase, the isolation relay 21 is ablated, i.e. the catheter electrode and the outer electrode 1 are disconnected from the impedance measurement circuit 17 under control of the PC. An ablation isolation grounding relay 20 connects the catheter electrode and the external electrode terminal of the N-way switch 18 to ground.

Ablation shunt relay 19 and ablation isolation relay set 22 provide RF ablation energy from RF generator 12 to catheter tip radiator electrode E1, patient return electrode 2 to provide an electrical return path. RF ablation energy is applied for a suitable time to thereby heat the tissue to initiate lesion formation. In experimental testing, the selection was made according to various factors including the patient's respiratory rate, so as to select an ablation duration of 5.2 seconds, as discussed in more detail below.

After each ablation stage, switching RF generator 12 from catheter tip electrode E1 and patient return electrode 2 to dummy load 25 using a relay circuit; a pause of 50ms when this switch occurs provides time for thermal equilibrium for the area around the developing lesion. During this time, the heated peripheral venous or arterial fluid/blood flows away from the catheter tip area during the ablation stage so that any thermal changes are only present in the lesion.

Measuring phase

The measurement phase 44 is used to measure the resulting voltage as current is applied from the routed inner electrodes to the outer electrodes as the ablation treatment progresses (i.e., between successive ablation cycles), thereby providing a measurement of the size of the lesion. After a 50ms delay at the end of the ablation stage, RF generator 12 switches from catheter tip electrode E1 and patient return electrode 2 to virtual load 25.

Under control of the PC, switch matrix 16 is connected to enable continuous four-terminal voltage measurements for the 10 measurement paths selected in determination stage 42.

The flow chart of fig. 5 provides further details of the measurement phase 44. Since the tissue impedance will drop with increasing temperature due to ablation within the tissue, the impedance value should be ignored if any of the 10 impedance measurements shows an increase in impedance between the present measurement and the last measurement (in the setup phase or the last measurement phase). An increase in impedance may indicate that the path has a low signal-to-noise ratio (SNR), or that the measurement is dominated by an accident or noise.

Referring to fig. 5, the measurement phase process begins with the first measurement path (i.e., path i equal to 1) (step 50). Under control of the PC, the switch matrix 16 is configured to make a single four-terminal voltage measurement (step 51) of the first path identified in decision step 42, which is used to determine the impedance. This value is then compared to the stored previous value in a decision (decision) step 52. If this new impedance measurement of the first path is lower than the previous value, this measurement will be used (step 53) as an indication of the size of the lesion. If the new impedance measurement is higher than the previous value, the value is discarded (step 54).

The next path is then measured and determined for impedance by incrementing the count (i + 1; step 58) and repeating the process. Decision step 59 determines whether all 10 paths have been measured, at which point the process moves to decision step 57. If it is determined that none of the 10 impedance values is below its previous measurement, the lesion may be considered to be of the same size as the previous cycle (step 55). This may indicate ablation failure and need to be repeated, however, towards the end of the ablation process, an equilibrium state is reached and the lesion no longer grows significantly. Of course, the decision to continue ablation will be made by the cardiologist/surgeon based on the notification by the impedance measurements.

If it is determined (step 57) that at least one impedance measurement has been flagged as used (i.e., the impedance of that particular path has decreased, indicating an increase in lesion size), the PC uses the impedance measurements to make a lesion size determination (step 56) using a predefined set of impedance depth and width curves.

To exclude possible underestimates and overestimates, the quantiles of depth and width groups of the cumulative probability of 0.45 to 0.55 are used to constrain the results. These may be extended to 0.35 to 0.65, then 0.25 to 0.75 at maximum until at least one measurement is found to fall within this range. Thus, the final measured lesion size will represent the average depth and width.

FIG. 9 provides a schematic illustration of catheter 3 in which electrodes E1, E2, E3, E4 are adjacent to lesion 90 in tissue 91, the width and height of the lesion being determined by the method of the present invention.

Returning to fig. 4, after the measurement phase 44, a determination of the lesion size after the most recent ablation cycle is made. At decision step 45, if the lesion is determined to have the desired size, the ablation treatment process ends. If the desired lesion size has not been reached, the surgeon/cardiologist may decide to start the next ablation iteration, so the process returns to the ablation stage 43.

As will be appreciated, this repeated alternation of ablation and impedance measurement cycles provides real-time continuous monitoring of the course of treatment, but the RF field does not interfere with the measurement device (or vice versa).

Example 2

In this alternative embodiment, the circuitry of the electrical interface module 6A connected to the RF generator 12A is shown in FIG. 3. The ablation shunt relay 19A and the relays of the relay sets 31 and 32 are shown in an impedance measurement position. The N-way switches of switch matrix 16A are shown set to arbitrary positions, however during the measurement phase the switches will again cycle through multiple positions.

Switch matrix 16A is comprised of a plurality of N-way steering switches 30 and 30A through 30X. Unlike the arrangement of embodiment 1, I + of the current source is not connected to the four-way switch, but is only connected to electrode E2 via an ablation isolation relay, and V + is similarly only connected to catheter tip electrode E1 via an ablation isolation relay. The poles of the steering switch 30 are connected to the I-terminal of the current source, and the poles of the switches 30A-30X are connected to the V-terminals of a plurality of analog-to-digital converters (ADCs) 14A-14X.

In this embodiment, the inventors' improvement in the apparatus, particularly in providing more reliable fast switching to isolate the RF generator from the catheter, means (unlike embodiment 1) that the catheter tip electrode E1 can be used as an impedance measuring electrode. This is preferred because E1 is the catheter electrode closest to the ablation region.

For ease of illustration, only three terminals of the N-way switch are shown. The throws of the switches 30 to 30X are connected to the outer point electrodes 1 to N of the electrode belt 4. In the present embodiment, the N-way steering switch of the measurement circuit 17A allows four-terminal impedance measurements to be made in parallel, thereby reducing the length of time required to measure all impedance paths (in this embodiment, 416 paths in total).

During the measurement phase, the I-terminal of the current source is connected sequentially to each of the outer point electrodes, while the V-terminal(s) are connected to the adjacent point electrode at the position of the current source I-terminal. For example, measurement circuit 17A may include 8 ADCs (ADC1-ADC8) with 8 corresponding N switches 30A-30H, and thus a total of 9N switches (including switch 30) in switch matrix 16A. As will be appreciated, in this way, for each I-terminal position of the AC current source 15, all 8 adjacent electrodes can be measured simultaneously, thus significantly reducing the total sampling time.

The ablation shunt relay 19A is an SPDT (single pole double throw) relay, as used in example 1, which again operates simultaneously to direct electrical ablation power from the RF generator 12A onto the catheter electrode E1 and the return electrode 2, or onto the dummy load 25 (e.g., a 10 Ω resistor) while a measurement is being performed. This arrangement provides protection for the measurement circuit 17A and other components from high voltage and RF noise.

Further, the grounding relay 31 is arranged to operate in synchronization with the ablation shunt relay 19A. Thus, ablation shunt relay 19A and ground relay 31 enable the system to switch between two states (i.e., an ablation state and a measurement state). Again, the method involves an iterative process that loops between these two states, as discussed below with reference to fig. 6.

To avoid noise from RF generator 12A in the impedance measurement, the relays of relay set 32 disconnect catheter electrodes E2-E4 from the RF generator during the measurement phase. However, during the ablation stage, the physician may use signals from E2, E3, and E4 to confirm the catheter position, although the position determination does not form part of the present invention.

The process of selecting 10 measurement paths described above with reference to embodiment 1 aims to reduce the measurement cycle time. This is particularly relevant if the impedance measurement may be affected by power line disturbances and the measurement duration has to be chosen to take such disturbances into account. For example, a duration of 5 powerline cycles may be suitable to reduce the effect of interference. For a 50Hz mains frequency, the time for one measurement (measurement period) may therefore be 100ms (5 × 1/50 Hz). In the case where power line interference is not significant, the inventors have determined that a measurement duration of 2.5ms is suitable.

Thus, in the present embodiment, the shorter measurement interval in combination with the use of parallel switching allows all N electrodes to be used in each measurement phase without undesirably interrupting the ablation process. The particular connection mode in which this occurs may be arranged by the sequencer to allow a minimum number of changes per switch position. To this end, very fast solid state switches are used for the N-way switches 30A-30X.

In this embodiment, since all path impedances are measured in the measurement phase (rather than a preselected subset of paths), there is no need to perform a separate setup phase. This process is shown in fig. 6, which depicts a loop between the measurement phase 64 and the ablation phase 63, the determination step 65 being used to decide when to stop the ablation process.

Measuring phase

In the measurement phase 64, voltage measurements resulting from the applied current are obtained and recorded for the electrical paths between the selected catheter electrodes (in this case E1 and E2) and all the outer electrodes 1.

As described above, four-terminal voltage measurements are made for each outer point electrode 1 a plurality of times with respect to all adjacent electrodes. In the configuration of fig. 8 (band 4 consists of 64 electrodes arranged in four rows of 16 electrodes each), a total of 416 impedance measurements and paths are recorded (five for each electrode in the top and bottom bands and eight for each electrode in the middle band). In the case of eight ADCs, all eight electrodes adjacent to the outer spot electrode 1 can be measured in a single cycle. Thus, for a single measurement duration of 2.5ms, the duration of a complete measurement cycle will be 160ms (2.5ms × 64 ═ 160 ms). As will be appreciated, in this case three of the eight ADCs will record empty measurements for the top and bottom row electrodes, which are automatically excluded from the recording/analysis.

The flowchart of fig. 7 provides further details of the measurement phase 64. As will be appreciated, the various steps of the process are the same as described above with reference to fig. 6 (and will not be described in detail here), however in embodiment 2 all impedance paths are measured and processed, rather than a preselected subset of the paths.

Note that although only the results of the current path in which the measurement shows a decrease in impedance are used (step 54A), the results of the current path in which the impedance path measurement increases may also be processed to provide additional information. For example, such a result may indicate that the catheter has moved between successive measurements.

At step 71, the previous Z for each measurement is calculated_istartAnd current Z_icurrentDifference value Δ Z therebetween_i. Measuring the mean slope (slope) Δ Z/Δ t in the first 30 seconds of ablation_30sec(measured in ohms/sec). At step 72, each measurement is calibrated using the following equation:

the results are then subjected to further appropriate processing (in particular, regression analysis) to determine lesion size (and other characteristics). In particular, some or all of the calibrated measurements are then used at step 73 to determine lesion size and orientation. The measurements from each cycle were regressed with respect to time to provide a logarithmic heat rise curve for determining the size of the lesion. Orientation may be determined by correlating lesion size with external spot electrode location. This method eliminates the need for known impedance versus depth and impedance versus width curves as described above with reference to example 1.

As will be appreciated, the selection of the particular impedance measurement to be processed (and the particular calibrated measurement to be analyzed) among all impedance measurements made will depend on a variety of different factors. The selection may be made under the control of computer software according to prescribed criteria (on a dynamic basis, if desired).

As schematically shown in fig. 6, once the lesion size is determined after the most recent ablation cycle, the ablation treatment process ends (if the lesion is determined to have the desired size) or (if it does not have the desired size) the next iteration of ablation and measurement begins at decision step 65. As will be appreciated, the determination step 65 may be bypassed after the initial measurement phase, before any ablation therapy has been applied.

Once ablation is interrupted, further cycles of the impedance measurement phase can be performed in order to monitor the bounce of the impedance values. While the change in impedance due to changes in tissue composition and structure is permanent, the change in impedance due to temperature is not permanent. Thus, this post-ablation monitoring allows the generation and analysis of impedance recovery curves, providing valuable information about the mechanism and characteristics of the ablation performed.

The above examples of the invention relate to four-terminal impedance measurement techniques, which are convenient methods in low impedance sensing and avoid measurement errors due to contact and/or wire resistance. However, readers of skill in the art will appreciate that the present invention may be implemented using other technologies, such as 2-terminal or 3-terminal approaches.

Furthermore, in any of the above embodiments, the impedance measurements may be gated by the patient's respiratory cycle and ECG to provide measurements taken at relatively stable points. In this respect, the point of stability is considered to be the point in time 200ms after the first QRS following the "lung empty" indication from the ventilator 100. In particular, after the ablation stage, at the next stable point, the generator 12 is disconnected from the catheter and switched to the virtual load 25, thereby making an impedance measurement. The duration of a typical ablation phase may be 3-5 seconds (within one respiratory cycle). Where the patient's breathing rate is about 12/m (i.e., 5s) and a typical ablation procedure takes between 30 and 90 seconds, this will involve about 6-18 ablation/measurement cycles. As the skilled reader will appreciate, alternative methods are possible. For example, multiple measurements (for all impedance paths) may be taken for each respiratory cycle, ideally gated by the patient's ECG.

As described elsewhere in this specification, although the described and illustrated embodiments conveniently use electrodes applied to the exterior of the patient's body to provide current conduction terminals, other locations within the patient's body may also be suitable, as long as they are sufficiently remote from the catheter electrode and in contact with the patient. For example, these "external" electrodes may be suitably placed within the esophagus and/or coronary sinus. When using such methods, an electroanatomical mapping system may be integrated with CT/MRI imaging to accurately determine the location of these "external electrode" sites within the anatomical volume.

Furthermore, the above description relates to RF ablation, but the method may also be used with other catheter ablation techniques (such as microwave radiation ablation). In such embodiments, the microwave radiation guide may be equipped with one or more suitably placed electrodes, such as a saline electrode or a conventional metal electrode.

As used herein, unless the context requires otherwise, the term "comprise" and variations of the term, such as "comprises," "comprising," and "having," are not intended to exclude other additives, components, integers, or steps.

Claims

1. A system for monitoring the development of tissue lesions during a medical ablation procedure applied to a patient, the system comprising:

a catheter ablation device having at least one catheter electrode;

a plurality of external electrodes for application to the patient's body;

a measurement circuit for determining an electrical characteristic of a current path between the at least one catheter electrode and the outer electrode without application of the ablation energy; and

an electrical controller.

2. The system of claim 1, wherein the electrical characteristic is an impedance of the current path.

3. The system of claim 2, wherein:

the electrical controller is arranged to control application of an AC current source between different combinations of the at least one catheter electrode and the plurality of external electrodes such that measurement of the resulting voltages provides a measurement of the impedance of different electrical paths through the patient's body between the respective electrodes; and

wherein the electrical controller is further configured to disconnect or otherwise suspend the catheter ablation device from the source of electrical energy during application of the AC current source.

4. The system of any one of the preceding claims, comprising a virtual resistive load for selectively connecting to the source of electrical energy during an operational period of the measurement circuit.

5. A system according to claim 3 or claim 4, wherein the measurement circuitry comprises a switch matrix arranged for switching between different combinations of electrodes under control of the electrical controller.

6. The system of any one of the preceding claims, wherein the measurement circuit is configured to perform four terminal sensing to measure the electrical characteristic.

7. The system of any one of the preceding claims, comprising a plurality of analog-to-digital converters (ADCs) for measuring different current paths simultaneously.

8. The system of any one of the preceding claims, wherein the source of electrical energy is an RF generator.

9. The system according to any one of the preceding claims, wherein the plurality of external electrodes are provided as electrode point ligaments for applying across an external region of the patient's body.

10. A method of operating a system for monitoring the size of a lesion during a catheter ablation procedure applied to tissue of a subject, the method comprising:

(b) performing a measurement phase involving measuring an electrical characteristic of a current path through a lesion region formed by the ablation;

wherein steps (a) and (b) are repeated sequentially.

11. The method of claim 10, wherein steps (a) and (b) are repeated sequentially until the measurements performed in step (b) indicate a specified lesion size.

12. The method of claim 10 or claim 11, wherein in step (b), ablation energy is transferred from the catheter-electrode to a virtual load.

13. The method of any one of claims 10 to 12, comprising using the system of any one of claims 1 to 9, performing step (a) using the catheter ablation device, performing step (b) using the plurality of external electrodes and the measurement circuitry, switching between steps (a) and (b) under control of the electrical controller.

14. The method according to any one of claims 10 to 13, comprising an initial determination phase in which one or more current paths are selected from a plurality of current paths by sequentially applying a current between one or more catheter electrodes and a plurality of electrodes applied outside the patient's body and measuring the electrical response, and the electrode for step (b) is selected in dependence on the result.

15. The method of claim 14, wherein a prescribed number of current paths are selected in the determination phase, with associated electrodes being used for subsequent iterations of step (b).

16. A method according to claim 14 or claim 15, wherein the electrodes are selected to be those associated with the lowest impedance of the measured current path.

17. The method of claim 14 or claim 15, wherein the electrodes are selected to be those associated with current paths that are most sensitive to local state changes of the patient's body, such as injecting a conductive solution into a region adjacent to the lesion.

18. The method of any one of claims 10 to 17, wherein the measurements obtained in step (b) are used in an algorithm to estimate the size of the lesion formed in step (a).

19. A method according to claim 18, wherein for each measurement phase, the measurements are analysed and a selection is made as to which measurements are used in the algorithm.

20. The method of claim 19, wherein selecting is based at least in part on a change in an electrical characteristic of the associated current path since a previous measurement phase.

21. The method of any one of claims 10 to 20, wherein step (a) and/or step (b) is gated by the subject's respiratory cycle and/or heartbeat.